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Publicaciones del Departamento de Histología y Embriología
Thy1-YFP-H Mice and the Parallel Rod Floor Test to Evaluate Short- and Long-Term Progression of Traumatic Brain Injury
Curr Protoc Immunol 2018 120:24.1.1-24.1.25
Monique Richter 1 2 , María Luciana Negro-Demontel 3 4 , Daniela Blanco-Ocampo 5 , Eliseo Taranto 5 , Natalia Lago 3 , Hugo Peluffo 3 4
1 Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay. 2 Current Address: Roche Diagnostics GmbH, Penzberg, Germany. 3 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay. 4 Department of Histology and Embryology, Faculty of Medicine, Universidad de la República, Montevideo, Uruguay. 5 Department of Physiopathology, Faculty of Medicine, Universidad de la República, Montevideo, Uruguay.
DOI: 10.1002/cpim.42
PMID: 29512144
Pubmed: https://pubmed.ncbi.nlm.nih.gov/29512144
Texto completo: https://doi.org/10.1002/cpim.42
Abstract:
Traumatic brain injury (TBI) is a leading cause of death and disability and is a risk factor for the later development of neuropsychiatric disorders and neurodegenerative diseases. Many models of TBI have been developed, but their further refinement and a more detailed long-term follow-up is needed. We have used the Thy1-YFP-H transgenic mouse line and the parallel rod floor test to produce an unbiased and robust method for the evaluation of the multiple effects of a validated model of controlled cortical injury. This approach reveals short- and long-term progressive changes, including compromised biphasic motor function up to 85 days post-lesion, which correlates with neuronal atrophy, dendrite and spine loss, and long-term axonal pathology evidenced by axon spheroids and fragmentation. Here we present methods for inducing a controlled cortical injury in the Thy1-YFP-H transgenic mouse line and for evaluating the resulting deficits in the parallel rod floor test. This technique constitutes a new, unbiased, and robust method for the evaluation of motor and behavioral alterations after TBI. © 2018 by John Wiley & Sons, Inc.
Kinesin 1 regulates cilia length through an interaction with the Bardet-Biedl syndrome related protein CCDC28B
Sci Rep 2018 8(1):3019
Rossina Novas 1 , Magdalena Cardenas-Rodriguez 1 , Paola Lepanto 1 , Matías Fabregat 1 , Magela Rodao 2 , María Inés Fariello 3 4 , Mauricio Ramos 5 , Camila Davison 2 , Gabriela Casanova 2 , Lucía Alfaya 6 , Federico Lecumberry 3 5 , Gualberto González-Sapienza 6 , Florencia Irigoín 1 7 , Jose L Badano 8
1 Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, CP11400, Uruguay. 2 Unidad de Microscopía Electrónica, Facultad de Ciencias, Iguá 4225, Montevideo, CP11400, Uruguay. 3 Facultad de Ingeniería, Universidad de la República, Julio Herrera y Reissig 565, Montevideo, CP11300, Uruguay. 4 Bioinformatics Unit, Institut Pasteur de Montevideo, Montevideo, Uruguay. 5 Signal Processing Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay. 6 Cátedra de Inmunología, DEPBIO, Facultad de Química, Universidad de la República, Av. Alfredo Navarro 3051, Montevideo, Uruguay. 7 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Gral. Flores 2125, Montevideo, CP11800, Uruguay. 8 Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, CP11400, Uruguay. jbadano@pasteur.edu.uy.
DOI: 10.1038/s41598-018-21329-6
PMID: 29445114
Pubmed: https://pubmed.ncbi.nlm.nih.gov/29445114
Texto completo: https://doi.org/10.1038/s41598-018-21329-6
Abstract:
Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal disease and mental retardation. CCDC28B is a BBS-associated protein that we have previously shown plays a role in cilia length regulation whereby its depletion results in shortened cilia both in cells and Danio rerio (zebrafish). At least part of that role is achieved by its interaction with the mTORC2 component SIN1, but the mechanistic details of this interaction and/or additional functions that CCDC28B might play in the context of cilia remain poorly understood. Here we uncover a novel interaction between CCDC28B and the kinesin 1 molecular motor that is relevant to cilia. CCDC28B interacts with kinesin light chain 1 (KLC1) and the heavy chain KIF5B. Notably, depletion of these kinesin 1 components results in abnormally elongated cilia. Furthermore, through genetic interaction studies we demonstrate that kinesin 1 regulates ciliogenesis through CCDC28B. We show that kinesin 1 regulates the subcellular distribution of CCDC28B, unexpectedly, inhibiting its nuclear accumulation, and a ccdc28b mutant missing a nuclear localization motif fails to rescue the phenotype in zebrafish morphant embryos. Therefore, we uncover a previously unknown role of kinesin 1 in cilia length regulation that relies on the BBS related protein CCDC28B.
A Rapid and Efficient Method to Dissect Pupal Wings of Drosophila Suitable for Immunodetections or PCR Assays
J Vis Exp 2017 (130):55854
Carmen Bolatto 1 , Cristina Parada 2 , Victoria Colmenares 2
1 Departamento de Histología y Embriología, Facultad de Medicina, Laboratorio de Biología del Desarrollo; cbolatto@fmed.edu.uy. 2 Departamento de Histología y Embriología, Facultad de Medicina, Laboratorio de Biología del Desarrollo.
DOI: 10.3791/55854
PMID: 29364201
Pubmed: https://pubmed.ncbi.nlm.nih.gov/29364201
Texto completo: https://doi.org//10.3791/55854
Abstract:
Wing development in Drosophila melanogaster is an ideal model for studying morphogenesis at tissue level. These appendages develop from a group of cells named wing imaginal discs formed during embryonic development. In the larval stages the imaginal discs grow, increasing its number of cells and forming monolayered epithelial structures. Inside the pupal case, the imaginal discs bud out and fold into bilayers along a line that becomes the future margin of the wing. During this process, the longitudinal primodia veins originate vein cells on the prospective dorsal and ventral surfaces of the wing. During the pupal stage the stripes of vein cells of each surface communicate in order to generate tight tubes; at the same time, the cross-veins begin their formation. With the help of appropriate molecular markers, it is possible to identify the major elements composing the wing during its development. For this reason, the ability to accurately detect transcripts or proteins in this structure is critical for studying their abundance and localization related to the development process of the wing. The procedure described here focuses on manipulating pupal wings, providing detailed instructions on how to dissect the wing during the pupal stage. The dissection of pupal tissue is more difficult to perform than their counterparts in third instar larvae. This is why this approach was developed, to obtain rapid and efficient high quality samples. Details of how to immunostain and mount these wing samples, to allow the visualization of proteins or cell components, are provided in the protocol. With little expertise it is possible to collect 8-10 high quality pupal wings in a short amount of time.
Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis
Sci Rep 2017 7(1):13544
Águeda Martínez-Barriocanal 1 2 , Andrea Arcas-García 1 , Miriam Magallon-Lorenz 1 , Aroa Ejarque-Ortíz 1 , María Luciana Negro-Demontel 3 4 , Emma Comas-Casellas 1 , Simo Schwartz Jr 5 2 , Sunny Malhotra 3 , Xavier Montalban 3 , Hugo Peluffo 4 6 , Margarita Martín 7 , Manuel Comabella, Joan Sayós 8 9
1 CIBBIM-Nanomedicine-Immune Regulation and Immunotherapy Group. Institut de Recerca Vall Hebrón (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 2 Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain. 3 Servei de Neurologia-Neuroimmunologia. Centre d'Esclerosi Múltiple de Catalunya (Cemcat). Institut de Recerca Vall Hebrón (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 4 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur Montevideo, Montevideo, Uruguay. 5 CIBBIM-Nanomedicine-Drug Delivery and Targeting Group. Institut de Recerca Vall Hebrón (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 6 Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay. 7 Biochemistry Unit, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Faculty of Medicine, University of Barcelona, Barcelona, Spain. 8 CIBBIM-Nanomedicine-Immune Regulation and Immunotherapy Group. Institut de Recerca Vall Hebrón (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. joan.sayos@vhir.org. 9 Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain. joan.sayos@vhir.org.
DOI: 10.1038/s41598-017-12881-8
PMID: 29051512
Pubmed: https://pubmed.ncbi.nlm.nih.gov/29051512
Texto completo: https://doi.org/10.1038/s41598-017-12881-8
Abstract:
Herein, we have used bioinformatics tools to predict five clusters defining ligand-binding sites on the extracellular domain of human CD300b receptor, presumably involved in the formation of both homodimers and heterodimers with other CD300 family members. Site-directed mutagenesis revealed residues glutamic acid 28 and glutamine 29 in cluster 5 to be necessary for the formation of CD300b complexes. Surprisingly, the disruption of cluster 2 and 4 reconstituted the binding capability lost by the mutation of residues glutamic acid 28 to alanine, glutamine 29 to alanine (E28A-Q29G). We identified a missense mutation arginine 33 to glutamine (R33Q) in CD300f by direct sequencing of exon 2 in peripheral blood samples from 50 patients with multiple sclerosis (MS). Levels of expression of CD300f were almost undetectable on monocytes from the patient bearing the R33Q mutation compared with healthy individuals. Whereas R33Q mutation had no effect in the formation of CD300f complexes, the inhibition of protein synthesis with cycloheximide indicated that CD300f R33Q is less stable than native CD300f. Finally, we report that the levels of expression of CD300f on the surface of classical and intermediate monocytes from MS patients are significantly lower when compared to the same cell populations in healthy individuals.
Stem cells distribution, cellular proliferation and migration in the adult Austrolebias charrua brain
Brain Res 2017 1673:11-22
Maximiliano Torres-Pérez 1 , Juan Carlos Rosillo 2 , Ines Berrosteguieta 3 , Silvia Olivera-Bravo 4 , Gabriela Casanova 5 , José Manuel García-Verdugo 6 , Anabel Sonia Fernández 7
1 Departamento NCIC, Neuroanatomía Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay. Electronic address: mtorres@iibce.edu.uy. 2 Departamento NCIC, Neuroanatomía Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay; Departamento de Histología y Embriología de la Facultad de Medicina UdelaR, Avda. General Flores 2125, 11800 Montevideo, Uruguay. Electronic address: jrosillo@iibce.edu.uy. 3 Departamento NCIC, Neuroanatomía Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay. 4 Neurobiología Celular y Molecular, Instituto de Investigaciones Biológicas "Clemente Estable" (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay. Electronic address: solivera@iibce.edu.uy. 5 Unidad de Microscopia Electrónica, Facultad de Ciencias, Universidad de la República (UdelaR), Iguá 4225, 11400 Montevideo, Uruguay. Electronic address: casanova@fcien.edu.uy. 6 Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, Paterna 46980, CIBERNED, Spain. Electronic address: j.manuel.garcia@uv.es. 7 Departamento NCIC, Neuroanatomía Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600 Montevideo, Uruguay; Neuroanatomía Comparada, Unidad Asociada a la Facultad de Ciencias, Universidad de la República (UdelaR), Iguá 4225, 11400 Montevideo, Uruguay. Electronic address: anabelsonia@gmail.com.
DOI: 10.1016/j.brainres.2017.08.003
PMID: 28797690
Pubmed: https://pubmed.ncbi.nlm.nih.gov/28797690
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(17)30330-X
Abstract:
Our previous studies demonstrated that Austrolebias charrua annual fish is an excellent model to study adult brain cell proliferation and neurogenesis due to the presence of active and fast neurogenesis in several regions during its short lifespan. Our main goal was to identify and localize the cells that compose the neurogenic areas throughout the Austrolebias brain. To do this, we used two thymidine halogenated analogs to detect cell proliferation at different survival times: 5-chloro-2'-deoxyuridine (CldU) at 1day and 5-iodo-2'-deoxyuridine (IdU) at 30days. Three types of proliferating cells were identified: I - transient amplifying or fast cycling cells that uptake CldU; II - stem cells or slow cycling cells, that were labeled with both CldU and IdU and did not migrate; and III - migrant cells that uptake IdU. Mapping and 3D-reconstruction of labeled nuclei showed that type I and type II cells were preferentially found close to ventricle walls. Type III cells appeared widespread and migrating in tangential and radial routes. Use of proliferation markers together with Vimentin or Nestin evidenced that type II cells are the putative stem cells that are located at the ventricular lumen. Double label cells with IdU+ and NeuN or HuC/D allowed us identify migrant neurons. Quantitation of labeled nuclei indicates that the proportion of putative stem cells is around 10% in all regions of the brain. This percentage of stem cells suggests the existence of a constant brain cell population in Austrolebias charrua that seems functional to the maintainance of adult neurogenesis.
Cell Proliferation, Migration, and Neurogenesis in the Adult Brain of the Pulse Type Weakly Electric Fish, Gymnotus omarorum
Front Neurosci 2017 11:437
Valentina Olivera-Pasilio 1 2 3 , Moira Lasserre 1 , María E Castelló 1 3
1 Desarrollo y Evolución Neural, Departamento de Neurociencias Integrativas y Computacionales, Instituto de Investigaciones Biológicas Clemente Estable, Ministerio de Educación y CulturaMontevideo, Uruguay. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la RepúblicaMontevideo, Uruguay. 3 IIBE "Histología de Sistemas Sensoriales", Unidad Asociada F. de MedicinaMontevideo, Uruguay.
DOI: 10.3389/fnins.2017.00437
PMID: 28860962
Pubmed: https://pubmed.ncbi.nlm.nih.gov/28860962
Texto completo: https://doi.org/10.3389/fnins.2017.00437
Abstract:
Adult neurogenesis, an essential mechanism of brain plasticity, enables brain development along postnatal life, constant addition of new neurons, neuronal turnover, and/or regeneration. It is amply distributed but negatively modulated during development and along evolution. Widespread cell proliferation, high neurogenic, and regenerative capacities are considered characteristics of teleost brains during adulthood. These anamniotes are promising models to depict factors that modulate cell proliferation, migration, and neurogenesis, and might be intervened to promote brain plasticity in mammals. Nevertheless, the migration path of derived cells to their final destination was not studied in various teleosts, including most weakly electric fish. In this group adult brain morphology is attributed to sensory specialization, involving the concerted evolution of peripheral electroreceptors and electric organs, encompassed by the evolution of neural networks involved in electrosensory information processing. In wave type gymnotids adult brain morphology is proposed to result from lifelong region specific cell proliferation and neurogenesis. Consistently, pulse type weakly electric gymnotids and mormyrids show widespread distribution of proliferation zones that persists in adulthood, but their neurogenic potential is still unknown. Here we studied the migration process and differentiation of newborn cells into the neuronal phenotype in the pulse type gymnotid Gymnotus omarorum. Pulse labeling of S-phase cells with 5-Chloro-2'-deoxyuridine thymidine followed by 1 to 180 day survivals evidenced long distance migration of newborn cells from the rostralmost telencephalic ventricle to the olfactory bulb, and between layers of all cerebellar divisions. Shorter migration appeared in the tectum opticum and torus semicircularis. In many brain regions, derived cells expressed early neuronal markers doublecortin (chase: 1-30 days) and HuC/HuD (chase: 7-180 days). Some newborn cells expressed the mature neuronal marker tyrosine hydroxylase in the subpallium (chase: 90 days) and olfactory bulb (chase: 180 days), indicating the acquisition of a mature neuronal phenotype. Long term CldU labeled newborn cells of the granular layer of the corpus cerebelli were also retrogradely labeled "in vivo," suggesting their insertion into the neural networks. These findings evidence the neurogenic capacity of telencephalic, mesencephalic, and rhombencephalic brain proliferation zones in G. omarorum, supporting the phylogenetic conserved feature of adult neurogenesis and its functional significance.
NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings
Brain Behav Immun 2017 64:367-383
Fernanda N Kaufmann 1 , Ana Paula Costa 1 , Gabriele Ghisleni 2 , Alexandre P Diaz 3 , Ana Lúcia S Rodrigues 1 , Hugo Peluffo 4 , Manuella P Kaster 5
1 Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. 2 Department of Life and Health Sciences, Catholic University of Pelotas, Rio Grande do Sul, Brazil. 3 Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil. 4 Neuroinflammation and Gene Therapy Lab., Institut Pasteur de Montevideo, Uruguay; Dept. Histology and Embryology, Faculty of Medicine, UDELAR, Uruguay. 5 Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address: manuella.kaster@ufsc.br.
DOI: 10.1016/j.bbi.2017.03.002
PMID: 28263786
Pubmed: https://pubmed.ncbi.nlm.nih.gov/28263786
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(17)30064-8
Abstract:
Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD). The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity. Recent data have demonstrated that NLRP3 activation appears to bridge the gap between immune activation and metabolic danger signals or stress exposure, which are key factors in the pathogenesis of psychiatric disorders. In this review, we discuss both preclinical and clinical evidence that links the assembly of the NLRP3 complex and the subsequent proteolysis and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in chronic stress models and patients with MDD. Importantly, we also focus on the therapeutic potential of targeting the NLRP3 inflammasome complex to improve stress resilience and depressive symptoms.
Associations between male infertility and ancestry in South Americans: a case control study
BMC Med Genet 2017 18(1):78
Maria Fernanda Skowronek 1 , Tatiana Velazquez 2 , Patricia Mut 2 , Gonzalo Figueiro 3 , Monica Sans 3 , Bernardo Bertoni 2 , Rossana Sapiro 4
1 Departamento de Histología y Embriología, Facultad de Medicina UDELAR, Montevideo, Uruguay. 2 Departamento de Genética, Facultad de Medicina UDELAR, Montevideo, Uruguay. 3 Departamento de Antropología, Facultad de Humanidades y Ciencias de la Educación, UDELAR, Montevideo, Uruguay. 4 Departamento de Histología y Embriología, Facultad de Medicina UDELAR, Montevideo, Uruguay. rsapiro@fmed.edu.uy.
DOI: 10.1186/s12881-017-0438-z
PMID: 28747152
Pubmed: https://pubmed.ncbi.nlm.nih.gov/28747152
Texto completo: https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-017-0438-z
Abstract:
Background: Infertility affects 15% of human couples, with men being responsible in approximately 50% of cases. Moreover, the aetiology of male factor infertility is poorly understood. The majority of male factor infertility remains idiopathic and potentially genetic in origin. The association of the Y chromosome and mitochondrial haplogroups with male infertility has been previously reported. This association differs between studied populations and their geographical distributions. These effects have been only rarely analysed in mixed populations, such as South Americans.
Methods: In this study, we analysed the contributions of the Y chromosome and mitochondrial haplogroups to male infertility in a mixed population. A case control study was conducted. Regular PCR and high-resolutionmelting- real-time PCR were performed to type haplogroups from fertile and infertile men. The sperm parameters from infertile men were compared in each haplogroup by logistic regression analysis and ANOVA.
Results: The genotyping confirmed the known admixture characteristic of the Uruguayan population. The European paternal contribution was higher than the maternal contribution in both fertile and infertile men. Neither maternal nor paternal ancestry presented differences between the cases and controls. Men belonging to the Y chromosome haplogroup F(xK) more frequently presented with an abnormal sperm morphology than men from other haplogroups. The sperm parameters were not associated with the mitochondrial haplogroups.
Conclusions: The data presented in this study showed an association between male infertility and ancestry in the Uruguayan population. Specifically, abnormal sperm morphology was associated with the Y chromosome haplogroup F(xK). Since the Y chromosome lacks recombination, these data suggest that some genes that determine sperm morphology might be inherited in blocks with the region that determines specific haplogroups. However, the possible association between the Y chromosome haplogroup F(xK) and sperm morphology requires further confirmatory testing. Data linking infertility with ancestry are needed to establish the possible causes of infertility and define male populations susceptible to infertility. Whether the admixed characteristics of the Uruguayan population exert any pressure on male fertility potential must be further investigated.
An immunohistochemical study on the distribution of vasotocin neurons in the brain of two weakly electric fish, Gymnotus omarorum and Brachyhypopomus gauderio
Tissue Cell 2017 49(2 Pt B):257-269
Paula Pouso 1 , Milka Radmilovich 2 , Ana Silva 3
1 Depto Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay; Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, Montevideo 11600, Uruguay. 2 Depto Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo 11800, Uruguay. 3 Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, Montevideo 11600, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay. Electronic address: asilva@fcien.edu.uy.
DOI: 10.1016/j.tice.2017.02.003
PMID: 28242105
Pubmed: https://pubmed.ncbi.nlm.nih.gov/28242105
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0040-8166(16)30317-2
Abstract:
Hypothalamic nonapeptides (arginin vasotocin-vasopressin, oxytocin-isotocin) are known to modulate social behaviors across vertebrates. The neuroanatomical conservation of nonapeptide systems enables the use of novel vertebrate model species to identify general strategies of their functional mechanisms. We present a detailed immunohistochemical description of vasotocin (AVT) cell populations and their projections in two species of weakly electric fish with different social structure, Gymnotus omarorum and Brachyhypopomus gauderio. Strong behavioral, pharmacological, and electrophysiological evidence support that AVT modulation of electric behavior differs between the gregarious B. gauderio and the solitary G. omarorum. This functional diversity does not necessarily depend on anatomical differences of AVT neurons. To test this, we focus on interspecific comparisons of the AVT system in basal non-breeding males along the brain. G. omarorum and B. gauderio showed similar AVT somata sizes and comparable distributions of AVT somata and fibers. Interestingly, AVT fibers project to areas related to the control of social behavior and electromotor displays in both species. We found that no gross anatomical differences in the organization of the AVT system account for functional differences between species, which rather shall depend on the pattern of activation of neurons embedded in the same basic anatomical organization of the AVT system.
Focal Transplantation of Aberrant Glial Cells Carrying the SOD1G93A Mutation into Rat Spinal Cord Induces Extensive Gliosis
Neuroimmunomodulation 2017 24(3):143-153
Sofía Ibarburu 1 , Emiliano Trias 1 , Natalia Lago 2 , Hugo Peluffo 2 3 , Romina Barreto-Núñez 1 , Valentina Varela 1 , Joseph S Beckman 4 , Luis Barbeito 1
1 Laboratorio de Neurodegeneración, Institut Pasteur de Montevideo, 2 Laboratorio de Neuroinflamación y Terapia Génica, Institut Pasteur de Montevideo, and 3 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; 4 Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
DOI: 10.1159/000480639
PMID: 29131016
Pubmed: https://pubmed.ncbi.nlm.nih.gov/29131016
Texto completo: https://doi.org/10.1159/000480639
Abstract:
Objective: We aimed to determine the potential of aberrant glial cells (AbAs) isolated from the spinal cord of adult SOD1G93A symptomatic rats to induce gliosis and neuronal damage following focal transplantation into the lumbar spinal cord of wild-type rats.
Methods: AbAs were obtained from the spinal cords of SOD1G93A symptomatic rats. One hundred thousand cells were injected using a glass micropipette into the lumbar spinal cords (L3-L5) of syngeneic wild-type adult rats. Equal volumes of culture medium or wild-type neonatal microglia were used as controls. Seven days after transplantation, immunohistochemistry analysis was carried out using astrocytic and microglia cell markers. Transplanted SOD1G93A AbAs were recognized by specific antibodies to human SOD1 (hSOD1) or misfolded human SOD1.
Results: Seven days after transplantation, AbAs were mainly detected in the medial region of the lumbar ventral horn as a well-limited cell cluster formed at the site of injection by their immunoreactivity to either misfolded SOD1 or normally folded hSOD1. Compared with controls, transplanted AbAs were surrounded by marked microgliosis and reactive astrocytes. Marked microgliosis was observed to extend bilaterally up to the cervical cord. Motor neurons close to AbA transplants were surrounded by activated glial cells and displayed ubiquitin aggregation.
Conclusions: AbAs bearing mutant SOD1G93A have the potential to induce neuroinflammation along the spinal cord and incipient damage to the motor neurons. The emergence of AbAs during amyotrophic lateral sclerosis pathogenesis may therefore be a mechanism to boost neuroinflammation and spread motor neuron damage along the neuroaxis.